Silent Information Regulator 2 (Sir2) protein is involved in transcriptional silencing and DNA damage repair in yeast. It also increases life span in yeast and in Caenorhabditis elegans. Yeast Sir2 protein has an NAD-dependent histone deacetylase activity that links Sir2 functions to cellular metabolism. This NAD-dependent deacetylase activity is conserved from bacteria to humans and mammalian Sir2 homologues also have NAD-dependent histone deacetylase activity. The NAD-dependency of Sir2-like enzymes distinguishes them from the class I and II HDAC histone deacetylases that use a zinc-catalyzed mechanism. Seven Sir2 homologues have been identified in humans and are designated hSIRT1-7. Among the human homologues, hSIRT1, hSIRT2 and hSIRT3 the most homologous to yeast Sir2 and have NAD-dependent deacetylase activity. At present, very little is known about the in vivo functions of mammalian SIR2 homologues. hSIRT1 deacetylates the transcription factor p53 thereby inhibiting p53 activation and apoptosis in response to DNA damage and oxidative stress.
Literature
Yang et al. (2000) Genomics 69:355-369; Frye (2000) Biochem. Biophys. Res. Comm. 273:793-798; GenBank Accession Nos. NM—012239 and AF083109.